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Podoplanin, ezrin, and Rho-A proteins may have joint participation in tumor invasion of lip cancer

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Abstract

Introduction

Podoplanin and ezrin connection through Rho-A phosphorylation have been suggested as part of the activation pathway, in the process of tumor invasion and cell movement in oral squamous cell carcinomas.

Objective

The aim of this study was to evaluate the correlation among podoplanin, ezrin, and Rho-A immunoexpressions in 91 squamous cells carcinomas of the lower lip and their influence in patient’s prognosis.

Material and methods

The immunoexpressions of podoplanin, ezrin, and Rho-A were evaluated through a semi-quantitative score method, based on the capture of 10 microscopic fields at the front of tumor invasion. The association and correlation of these proteins with the clinicopathological features were verified by Fischer’s exact test and Spearman’s test. The prognostic values were analyzed by Kaplan-Meier method and log-rank test.

Results

A statistically significant association between strong cytoplasmic podoplanin expression and alcohol (p = 0.024), loco-regional recurrences (p = 0.028), and lymph node metastasis (pN+) (p = 0.010) was found. The membranous (p = 0.000 and r = 0.384) and cytoplasmic (p = 0.000 and r = 0.344) podoplanin expression was statistically correlated with ezrin expression. Also, membranous podoplanin was significantly correlated with Rho-A expression (p = 0.006 and r = 0.282). The expressions of podoplanin, ezrin, and Rho-A were not significant prognostic factors for patients with squamous cell carcinomas of the lower lip.

Conclusions

Therefore, our results confirm a correlation among podoplanin, ezrin, and Rho-A expressions in squamous cell carcinoma of the lip suggesting a cooperative participation of these proteins in cell movement and invasion.

Clinical relevance

Furthermore, strong cytoplasmic podoplanin expression could be helpful to identify patients with squamous cell carcinoma of the lip and lower risk of loco-regional recurrences.

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Authors and Affiliations

  1. Department of Stomatology, Area of Pathology, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisola, 9-75, Bauru, SP, 17012-901, Brazil

    Agnes Assao & Denise Tostes Oliveira

  2. Adolfo Lutz Institute, Pathology Division, R. Professor Antônio Prudente, 211, Liberdade, São Paulo, SP, 01509 – 010, Brazil

    Suely Nonogaki

  3. Department of Community Dentistry, Bauru School of Dentistry, University of São Paulo, Al. Octávio Pinheiro Brisola, 9-75, Bauru, SP, 17012-901, Brazil

    José Roberto Pereira Lauris

  4. Fundação Pio XII Institution – Cancer Hospital of Barretos, R. Antenor Duarte Viléla, 1331, Barretos, SP, 14784-400, Brazil

    André Lopes Carvalho

  5. Department of Pathology, A.C. Camargo Cancer Hospital, R. Professor Antônio Prudente, 211, Liberdade, São Paulo, SP, 01509 – 010, Brazil

    Clóvis Antônio Lopes Pinto & Fernando Augusto Soares

  6. Department of Head and Neck Surgery and Otorhinolaryngology, Cancer Hospital A.C. Camargo, R. Professor Antônio Prudente, 211, Liberdade, São Paulo, SP, 01509 – 010, Brazil

    Luiz Paulo Kowalski

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  1. Agnes Assao
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  2. Suely Nonogaki
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  8. Denise Tostes Oliveira
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Correspondence to Denise Tostes Oliveira.

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Funding

This study was funded by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP – Grants #2013/16999-7 and #2012/13411-6).

Conflict of interest

The authors declare that they have no conflict of interests.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Committee of Ethics and Research of the Bauru School of Dentistry, University of São Paulo, has approved this study (process #551531/2014 – CAAE 01594912.2.0000.5417).

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Assao, A., Nonogaki, S., Lauris, J.R.P. et al. Podoplanin, ezrin, and Rho-A proteins may have joint participation in tumor invasion of lip cancer. Clin Oral Invest 21, 1647–1657 (2017). https://doi.org/10.1007/s00784-016-1956-3

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  • DOI: https://doi.org/10.1007/s00784-016-1956-3

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